What is the recommended treatment for hepatic encephalopathy?

Treatment of Hepatic Encephalopathy

Lactulose is the first-line treatment for hepatic encephalopathy, with rifaximin as an effective add-on therapy for prevention of recurrence. 1, 2, 3

Four-Pronged Approach to Management

• Initiate appropriate care for patients with altered consciousness, with intensive care monitoring for those with higher grades of HE who cannot protect their airway 1, 3
• Identify and treat alternative causes of altered mental status that may coexist with HE 1, 3
• Identify and correct precipitating factors, which can resolve HE in nearly 90% of patients 1, 2
• Commence empirical HE treatment without delay 1, 2

First-Line Treatment

• Start lactulose at 25 mL orally every 12 hours, titrated to achieve 2-3 soft bowel movements daily 2, 3
• Lactulose works by acidifying the gastrointestinal tract and inhibiting ammonia production by coliform bacteria 4, 5
• In patients unable to take oral medications, administer lactulose via nasogastric tube 1
• FDA-approved indication: "For the prevention and treatment of portal-systemic encephalopathy, including the stages of hepatic pre-coma and coma" 4

Second-Line and Add-On Treatments

• Add rifaximin 550 mg twice daily when lactulose alone fails to prevent recurrence of HE 1, 2, 6
• Rifaximin reduces the risk of HE recurrence by 58% when added to lactulose 2, 3
• FDA-approved indication for rifaximin: "Reduction in risk of overt hepatic encephalopathy recurrence in adults" 6
• In the clinical trials of rifaximin for HE, 91% of patients were using lactulose concomitantly 6

Alternative Treatments for Non-Responders

• Oral Branched-Chain Amino Acids (BCAAs) can be used for patients not responding to conventional therapy 1, 3
• IV L-Ornithine L-Aspartate (LOLA) is an alternative for patients not responding to conventional therapy 1
• Neomycin (4-12 grams daily in divided doses) can be considered as an alternative, but long-term use is limited by ototoxicity and nephrotoxicity 1, 7, 8
• Metronidazole is another alternative but has significant side effects with long-term use 1, 8

Prevention of Recurrence

• Secondary prophylaxis after an episode of overt HE is strongly recommended 1
• Lactulose is recommended for prevention of recurrent episodes 1, 9
• For patients with recurrent HE despite lactulose therapy, add rifaximin 550 mg twice daily 1, 6
• Long-term rifaximin treatment (>24 months) has shown a good safety profile for prevention of recurrence 2

Special Considerations

• Liver transplantation should be considered in patients with recurrent intractable HE and liver failure 1, 2
• For patients with preserved liver function and recurrent HE, evaluate for large spontaneous portosystemic shunts that may be amenable to embolization 1
• Neither rifaximin nor lactulose has been shown to prevent post-TIPS HE better than placebo; shunt diameter reduction may be necessary if severe HE occurs after TIPS 1

Nutritional Considerations

• Avoid protein restriction as it can worsen malnutrition and sarcopenia, which are risk factors for HE 1
• Encourage small meals distributed throughout the day and a late-night snack 1
• Avoid fasting periods which can worsen HE 1

Common Pitfalls to Avoid

• Overuse of lactulose can lead to complications such as aspiration, dehydration, hypernatremia, and perianal skin irritation 2
• Failure to identify and treat precipitating factors (infections, GI bleeding, electrolyte disturbances, medication non-compliance) will result in poor treatment response 1, 2, 3
• Relying solely on ammonia levels for diagnosis or monitoring; a normal value should prompt diagnostic reevaluation 1, 2
• Delaying empirical treatment while awaiting diagnostic confirmation can worsen outcomes 2, 3